4.7 Article

Prostate cancer polygenic risk score and prediction of lethal prostate cancer

Journal

NPJ PRECISION ONCOLOGY
Volume 6, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41698-022-00266-8

Keywords

-

Categories

Funding

  1. National Institutes of Health/National Cancer Institute [R01 CA175491, R01 CA244948]
  2. Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center [P30 CA008748]
  3. SPORE grant in Prostate Cancer [P50-CA92629]
  4. Sidney Kimmel Center for Prostate and Urologic Cancers
  5. Prostate Cancer Foundation
  6. Swedish Cancer Society [CAN 2017/559]
  7. Swedish Research Council [2016-02974]
  8. General Hospital in Malmo Foundation for Combating Cancer
  9. Office of Research Infrastructure of the National Institutes of Health [S10OD018522, S10OD026880]

Ask authors/readers for more resources

Polygenic risk scores (PRS) for prostate cancer incidence were evaluated and compared to PSA and a commercialized model in predicting lethal prostate cancer. The study found that PRS was associated with incident prostate cancer, but was not a stronger predictor of lethal disease compared to PSA. The combination of PRS and PSA did not contribute additional risk stratification for lethal prostate cancer.
Polygenic risk scores (PRS) for prostate cancer incidence have been proposed to optimize prostate cancer screening. Prediction of lethal prostate cancer is key to any stratified screening program to avoid excessive overdiagnosis. Herein, PRS for incident prostate cancer was evaluated in two population-based cohorts of unscreened middle-aged men linked to cancer and death registries: the Vasterbotten Intervention Project (VIP) and the Malmo Diet and Cancer study (MDC). SNP genotypes were measured by genome-wide SNP genotyping by array followed by imputation or genotyping of selected SNPs using mass spectrometry. The ability of PRS to predict lethal prostate cancer was compared to PSA and a commercialized pre-specified model based on four kallikrein markers. The PRS was associated with incident prostate cancer, replicating previously reported relative risks, and was also associated with prostate cancer death. However, unlike PSA, the PRS did not show stronger association with lethal disease: the hazard ratio for prostate cancer incidence vs. prostate cancer metastasis and death was 1.69 vs. 1.65 in VIP and 1.25 vs. 1.25 in MDC. PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death. These findings have implications for public health policies for delivery of prostate cancer screening. Focusing polygenic risk scores on clinically significant endpoints such as prostate cancer metastasis or death would likely improve clinical utility.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available